Imposed mutational meltdown as an antiviral strategy

Evolution. 2020 Dec;74(12):2549-2559. doi: 10.1111/evo.14107. Epub 2020 Oct 27.

Abstract

Following widespread infections of the most recent coronavirus known to infect humans, SARS-CoV-2, attention has turned to potential therapeutic options. With no drug or vaccine yet approved, one focal point of research is to evaluate the potential value of repurposing existing antiviral treatments, with the logical strategy being to identify at least a short-term intervention to prevent within-patient progression, while long-term vaccine strategies unfold. Here, we offer an evolutionary/population-genetic perspective on one approach that may overwhelm the capacity for pathogen defense (i.e., adaptation) - induced mutational meltdown - providing an overview of key concepts, review of previous theoretical and experimental work of relevance, and guidance for future research. Applied with appropriate care, including target specificity, induced mutational meltdown may provide a general, rapidly implemented approach for the within-patient eradication of a wide range of pathogens or other undesirable microorganisms.

Keywords: Antivirals; SARS-CoV-2; lethal mutagenesis; mutational meltdown; population genetics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Antiviral Agents / therapeutic use
  • COVID-19 / drug therapy*
  • COVID-19 / virology*
  • Evolution, Molecular
  • Extinction, Biological
  • Genetic Drift
  • Genome, Viral
  • Humans
  • Models, Genetic*
  • Mutagenesis
  • Mutation*
  • Pandemics
  • SARS-CoV-2 / genetics*
  • SARS-CoV-2 / pathogenicity
  • Selection, Genetic

Substances

  • Antiviral Agents